Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study

Abstract

Background: Immunocompromised patients may be at higher risk of mortality if hospitalised with Coronavirus Disease 2019 (COVID-19) compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death and how this risk changed over the pandemic.

Methods and findings: We included patients > = 19 years with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK prospective cohort study. We defined immunocompromise as immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination, and comorbidities. We used Bayesian logistic regression to explore mortality over time. Between 17 January 2020 and 28 February 2022, we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. In total, 29% (n = 6,499) of immunocompromised and 21% (n = 28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjusted OR 1.44, 95% CI [1.39, 1.50], p < 0.001). Not all immunocompromising conditions had the same risk, for example, patients on active cancer treatment were less likely to have their care escalated to intensive care (adjusted OR 0.77, 95% CI [0.7, 0.85], p < 0.001) or ventilation (adjusted OR 0.65, 95% CI [0.56, 0.76], p < 0.001). However, cancer patients were more likely to die (adjusted OR 2.0, 95% CI [1.87, 2.15], p < 0.001). Analyses were adjusted for age, sex, socioeconomic deprivation, comorbidities, and vaccination status. As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50 to 69 years was 88% for men and 83% for women, and for those >80 years was 99% for men and 98% for women. The study is limited by a lack of detailed drug data prior to admission, including steroid doses, meaning that we may have incorrectly categorised some immunocompromised patients as immunocompetent.

Conclusions: Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses, monoclonal antibodies, and nonpharmaceutical preventive interventions should be continually encouraged for this patient group.

Trial registration: ISRCTN 66726260.

Fig 1. Flow diagram of patients in the study.

The total number of participants entered into the ISARIC CCP-UK database, reasons for exclusion, and numbers of patients in each category of immunocompromise are shown. CCP-UK, Clinical Characterisation Protocol in the United Kingdom; COVID-19, Coronavirus Disease 2019; ISARIC, International Severe Acute Respiratory and emerging Infection Consortium.

Fig 2. Overlap between conditions giving rise to immunocompromise and illness severity.

(A) Overlap between immunocompromising conditions for all combinations where there are 20 patients or greater. (B) Illness severity over the course of the pandemic, measured using the 4C Mortality Score by immune status and pandemic wave. Pink bars: immunocompetent, green bars: immunocompromised. (C) Physiological components of the 4C Mortality Score stratified by immune status and pandemic wave.

Fig 3. Outcomes of hospitalised immunocompromised patients, compared with immunocompetent patients.

Odds ratios (ORs) from multivariable logistic regression and 95% confidence intervals (CIs) for outcomes of death, critical care admission, noninvasive and invasive ventilation, adjusted for age, sex, ethnicity, socioeconomic deprivation, chronic cardiac, pulmonary and renal disease, and vaccination status.

Fig 4. Outcomes of hospitalised immunocompromised patients, compared with immunocompetent patients over the first 4 pandemic waves in the UK.

Odds ratios (ORs) from multivariable logistic regression and 95% confidence intervals (CIs) for outcomes of death, broken down by pandemic wave, adjusted for age, sex, ethnicity, socioeconomic deprivation, comorbidity count (not including the immunocompromising condition), and vaccination status. Wave 1 was 17 January to 31 August 2020; wave 2 was 1 September 2020 to 31 March 2021; wave 3 was 1 April 2021 to 12 December 2021; and wave 4 was 13 December 2021 to 28 February 2022.

Fig 5. Absolute risk difference (ARD) for death between immunocompromised and immunocompetent.

The difference in risk of death in the first wave and the fourth wave for immunocompetent and immunocompromised patients was modelled using Bayesian logistic regression, and the probability that the risk of death across the two waves reduced more in the immunocompetent that the immunocompromised was calculated. The analysis was stratified by age and sex.